rs1519551

Variant names:

• chr4-141649319-G-A
• rs1519551
• NM_000585.5:c.-221-6867G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000585.5(IL15):​c.-221-6867G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,844 control chromosomes in the GnomAD database, including 23,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23612 hom., cov: 32)
• Consequence: IL15 NM_000585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 19 publications found

Genes affected

IL15 (HGNC:5977): (interleukin 15) The protein encoded by this gene is a cytokine that regulates T and natural killer cell activation and proliferation. This cytokine and interleukine 2 share many biological activities. They are found to bind common hematopoietin receptor subunits, and may compete for the same receptor, and thus negatively regulate each other's activity. The number of CD8+ memory cells is shown to be controlled by a balance between this cytokine and IL2. This cytokine induces the activation of JAK kinases, as well as the phosphorylation and activation of transcription activators STAT3, STAT5, and STAT6. Studies of the mouse counterpart suggested that this cytokine may increase the expression of apoptosis inhibitor BCL2L1/BCL-x(L), possibly through the transcription activation activity of STAT6, and thus prevent apoptosis. Alternatively spliced transcript variants of this gene have been reported. [provided by RefSeq, Feb 2011]

ENSG00000295574 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL15	NM_000585.5	c.-221-6867G>A		intron_variant	Intron 1 of 7	ENST00000320650.9	NP_000576.1
IL15	NM_172175.3	c.-623-6867G>A		intron_variant	Intron 1 of 9		NP_751915.1
IL15	NR_037840.3	n.643-6867G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL15	ENST00000320650.9	c.-221-6867G>A		intron_variant	Intron 1 of 7	1	NM_000585.5	ENSP00000323505.4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84022 AN: 151726 Hom.: 23608 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.537

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.554 AC: 84055 AN: 151844 Hom.: 23612 Cov.: 32 AF XY: 0.560 AC XY: 41551 AN XY: 74212

African (AFR) AF: 0.478 AC: 19776 AN: 41398

American (AMR) AF: 0.517 AC: 7879 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2320 AN: 3466

East Asian (EAS) AF: 0.850 AC: 4388 AN: 5164

South Asian (SAS) AF: 0.726 AC: 3497 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6543 AN: 10530

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37836 AN: 67906

Other (OTH) AF: 0.541 AC: 1138 AN: 2104

Alfa AF: 0.553 Hom.: 75154

Bravo AF: 0.537

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1519551; hg19: chr4-142570472;